PROJECT DESCRIPTION/ABSTRACT ? BIOMARKER CORE The overall goal of the Biomarker Core is to collect, bank, and distribute fluid and cellular biospecimens and generate biomarker datasets to address heterogeneity and improve diagnosis for Alzheimer's disease (AD) and AD-related dementias (ADRD). In doing so, the Biomarker Core will work closely with other Mayo ADRC Cores to address our overall theme to study the ?similarities and differences among neurodegenerative diseases?. During the past funding cycles, the Mayo ADRC has been in the forefront in improving diagnostic tools and defining clinical spectrum including normal aging, preclinical pathological changes, mild cognitive impairment (MCI), and ultimately disease onset and progression. In addition to imaging biomarkers, our center has been collecting and evaluating biomarkers measured in biospecimens including plasma, serum, and cerebral spinal fluid (CSF) to define changes in the course of dementia development and progression. To further support and accelerate the innovative discovery and translational research at Mayo Clinic and across the broad research community, we aim to establish this new Biomarker Core to systematically bank and distribute biospecimens. We also aim to generate and share critical biomarker datasets to enable research efforts in defining strategies for the early diagnosis, prevention and treatment of AD/ADRD. In addition to fluid biospecimens, the Biomarker Core will also collect, bank and distribute peripheral blood mononuclear cells (PBMCs), as well as PBMC-reprogrammed induced pluripotent stem cells (iPSCs). This innovative element of the Biomarker Core will built upon existing efforts and expertise through the Mayo Clinic Neuroregeneration Lab (MCNRL) where the Biomarker Core Leader Dr. Guojun Bu also serves as the Director. We propose four Specific Aims for the Biomarker Core. In Aim 1, we plan to bank and distribute plasma, serum and CSF samples from ADRC participants subjects by coordinating with the Clinical Core, and link sample information obtained through the Clinical, Neuroimaging, and Neuropathology Cores. Another activity of this Aim is to evaluate requests and distribute biospecimens through a Biospecimen Committee. In the second Aim, we plan to generate and publically share fluid biomarker datasets. Both validated and emerging biomarkers in plasma, serum and CSF will be measured by Mayo investigators or through collaboration and core services. In Aim 3, we plan to bank and distribute PBMCs for cellular biomarker discovery and for reprogramming to iPSCs. In Aim 4, we will convert selected PBMCs to iPSCs for banking, distribution and cellular biomarker discover. The reprogrammed iPSC lines will be selected based on research interests in the AD/ADRD community and will consider unique genetic backgrounds of the donors (e.g., APOE and TREM2 genotype). In addition to supplying iPSCs to investigators, the Biomarker Core will also provide technical assistant and training for differentiation of iPSCs to different brain cell types and brain organoids. Together, this comprehensive and innovative Biomarker Core will become an integral component of Mayo ADRC to enable the discovery and validation of fluid and cellular biomarkers.